title: Immunoregulation by Toxoplasma gondii infection prevents allergic immune responses in mice.
abstract: Toxoplasma gondii is a ubiquitous intracellular parasite affecting most mammals including humans. In epidemiological studies, infection with T. gondii and allergy development have been postulated to be inversely related. Using a mouse model of birch pollen allergy we investigated whether infection with T. gondii influences allergic immune responses to birch pollen. BALB/c mice were infected with T. gondii oocysts either before or at the end of sensitisation with the major birch pollen allergen Bet v 1 and thereafter aerosol challenged with birch pollen extract. During the acute phase of infection, clinical signs correlated with increased levels of serum TNF-alpha, IL-6, IFN-gamma and anti-Toxoplasma-IgM. In the chronic phase, Toxoplasma-specific serum IgG, brain tissue cysts and high IFN-gamma production in spleen cell cultures were detected. Mice infected prior to allergic sensitisation produced significantly less allergen-specific IgE and IgG1, while IgG2a levels were markedly increased. IL-5 levels in spleen cell cultures and bronchoalveolar lavage fluid were significantly reduced, and airway inflammation was prevented in these mice. Notably, in mice infected at the end of the allergic sensitisation process, systemic and local immune responses to the allergen were markedly reduced. T.gondii infection was associated with up-regulation of Toll-like receptor 2 (TLR2), 4, 9 and 11, as well as T-bet (a differentiation factor for Th1 cells) mRNA expression in splenocytes; moreover, enhanced TGF-beta, IL-10 and Foxp3 mRNA expression in these cells suggested that regulatory mechanisms were involved in suppression of the allergic immune response. Kinetic studies confirmed the induction of Foxp3(+)CD4(+)CD25(+) regulatory T cells preferentially during the chronic phase of T. gondii infection. Our data demonstrate that T. gondii exhibits strong immunomodulating properties which lead to prevention of allergic immune responses and thereby support the hygiene hypothesis.
authors.affiliation: Department of Specific Prophylaxis and Tropical Medicine, Center for Physiology, Pathophysiology & Immunology, Medical University of Vienna, Vienna, Austria.
authors.forename: Angelika
authors.initials: A
authors.lastname: Wagner
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Förster-Waldl
authors.forename: Erika
authors.initials: E
authors.lastname: Garner-Spitzer
authors.forename: Irma
authors.initials: I
authors.lastname: Schabussova
authors.forename: Michael
authors.initials: M
authors.lastname: Kundi
authors.forename: Arnold
authors.initials: A
authors.lastname: Pollak
authors.forename: Otto
authors.initials: O
authors.lastname: Scheiner
authors.forename: Anja
authors.initials: A
authors.lastname: Joachim
authors.forename: Ursula
authors.initials: U
authors.lastname: Wiedermann
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D029662:Betula / Q000276:immunology; D001921:Brain / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis*; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D007371:Interferon-gamma / Q000032:analysis; D015848:Interleukin-5 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D011058:Pollen / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000517:prevention & control; D013154:Spleen / Q000276:immunology; D051193:Toll-Like Receptors / Q000032:analysis; D014123:Toxoplasmosis / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000485:Allergens; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D015848:Interleukin-5; D015850:Interleukin-6; D012333:RNA, Messenger; D051193:Toll-Like Receptors; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma